May 10, 2021

Overview of presentation

  1. Introduction to COVID-19 World Vaccine Adverse Reactions Dataset

  2. Project work flow

  3. Project methods

    3.1 Overview of important packages and verbs used

    3.2 Challenges and solutions - Load, Clean and Augment

  4. Visualizations

  5. Modeling

  6. Conclusion and discussion

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Introduction

COVID-19 World Vaccine Adverse Reactions

Introduction

###COVID-19 World Vaccine Adverse Reactions

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COVID-19 World Vaccine Adverse Reactions

COVID-19 World Vaccine Adverse Reactions

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Introduction

###COVID-19 World Vaccine Adverse Reactions

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COVID-19 World Vaccine Adverse Reactions

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PATIENTS.CSV: Contains information about the individuals that received the vaccines

## # A tibble: 3 x 35
##   VAERS_ID RECVDATE  STATE AGE_YRS CAGE_YR CAGE_MO SEX   RPT_DATE   SYMPTOM_TEXT
##   <chr>    <chr>     <chr>   <dbl>   <dbl>   <dbl> <chr> <date>     <chr>       
## 1 0916600  01/01/20… TX         33      33      NA F     NA         "Right side…
## 2 0916601  01/01/20… CA         73      73      NA F     NA         "Approximat…
## 3 0916602  01/01/20… WA         23      23      NA F     NA         "About 15 m…
## # … with 26 more variables: DIED <chr>, DATEDIED <chr>, L_THREAT <chr>,
## #   ER_VISIT <chr>, HOSPITAL <chr>, HOSPDAYS <dbl>, X_STAY <chr>,
## #   DISABLE <chr>, RECOVD <chr>, VAX_DATE <chr>, ONSET_DATE <chr>,
## #   NUMDAYS <dbl>, LAB_DATA <chr>, V_ADMINBY <chr>, V_FUNDBY <chr>,
## #   OTHER_MEDS <chr>, CUR_ILL <chr>, HISTORY <chr>, PRIOR_VAX <chr>,
## #   SPLTTYPE <chr>, FORM_VERS <dbl>, TODAYS_DATE <chr>, BIRTH_DEFECT <chr>,
## #   OFC_VISIT <chr>, ER_ED_VISIT <chr>, ALLERGIES <chr>

Dimensions:

dim(patients)
## [1] 34121    35
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Introduction

###COVID-19 World Vaccine Adverse Reactions

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COVID-19 World Vaccine Adverse Reactions

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VACCINES.CSV: Contains information about the received vaccine

## # A tibble: 3 x 8
##   VAERS_ID VAX_TYPE VAX_MANU VAX_LOT VAX_DOSE_SERIES VAX_ROUTE VAX_SITE VAX_NAME
##   <chr>    <chr>    <chr>    <chr>   <chr>           <chr>     <chr>    <chr>   
## 1 0916600  COVID19  "MODERN… 037K20A 1               IM        LA       COVID19…
## 2 0916601  COVID19  "MODERN… 025L20A 1               IM        RA       COVID19…
## 3 0916602  COVID19  "PFIZER… EL1284  1               IM        LA       COVID19…

Dimensions:

dim(vaccines)
## [1] 34630     8
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Introduction

###COVID-19 World Vaccine Adverse Reactions

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COVID-19 World Vaccine Adverse Reactions

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SYMPTOMS.CSV: Contains information about the symptoms experienced after vaccination

## # A tibble: 3 x 11
##   VAERS_ID SYMPTOM1      SYMPTOMVERSION1 SYMPTOM2   SYMPTOMVERSION2 SYMPTOM3    
##   <chr>    <chr>                   <dbl> <chr>                <dbl> <chr>       
## 1 0916600  Dysphagia                23.1 Epiglotti…            23.1 <NA>        
## 2 0916601  Anxiety                  23.1 Dyspnoea              23.1 <NA>        
## 3 0916602  Chest discom…            23.1 Dysphagia             23.1 Pain in ext…
## # … with 5 more variables: SYMPTOMVERSION3 <dbl>, SYMPTOM4 <chr>,
## #   SYMPTOMVERSION4 <dbl>, SYMPTOM5 <chr>, SYMPTOMVERSION5 <dbl>

Dimensions:

dim(symptoms)
## [1] 48110    11
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Methods: Project workflow

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Project workflow

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  1. Load data sets (patients, vaccines, symptoms)
  2. Clean each data set individually
  3. Augment and merge the data sets
  4. Make visualizations
  5. Do modeling
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Methods: Important packages and verbs

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Project methods - Important packages and verbs

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Load and clean

  • readr: read_csv(), write_csv()
  • dyplyr: filter(), select(), distinct(), mutate()
  • tidyr: replace_na()

Augment

  • dplyr: filter(), select(), mutate(), case_when(), arrange(), group_by(), count(), distinct(), summarise(), drop_na(), rename()
  • tidyr: pivot_longer(), pivot_wider(), inner_join(), full_join(), pluck()
  • stringr: regular expressions, str_c(), str_replace(), str_replace()

Analysis

  • ggplot: geom_bar(), geom_boxplot(), geom_tile(), geom_segment(), theme_minimal()
  • forcats: fct_reorder()
  • scales
  • patchwork
  • viridis
  • stats (?): glm(), prcomp()
  • broom: tidy(), glance()
  • purrr: map(), nest()
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Methods: Dataset loading

Challenges and solutions

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Project methods - Challenges and solutions - 01_load

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Patients, vaccines and symptoms datasets:

  • Multiple large files → keep them compressed as gz-files and only decompress when reading into R
  • Wrong column types automatically assigned by R → manually assign appropriate column types
  • NA strings (“NA”, “N/A”, “Unknown”, " "…) → assign NAs when loading data
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Methods: Dataset cleaning

Challenges and solutions

Patients dataset:

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01_load - Challenges and Solutions 1 (DELETE SLIDE)

CHALLENGE 1: Multiple large files

SOLUTION: Keep them compressed and only decompress when reading into R:

01_load - Challenges and Solutions 2 (DELETE SLIDE)

CHALLENGE: Wrong column types automatically assigned by R

## Warning: 241 parsing failures.
##  row          col           expected     actual         file
## 1465 BIRTH_DEFECT 1/0/T/F/TRUE/FALSE Y          <connection>
## 2742 X_STAY       1/0/T/F/TRUE/FALSE Y          <connection>
## 2807 RPT_DATE     1/0/T/F/TRUE/FALSE 2021-01-04 <connection>
## 2807 V_FUNDBY     1/0/T/F/TRUE/FALSE OTH        <connection>
## 2811 RPT_DATE     1/0/T/F/TRUE/FALSE 2021-01-04 <connection>
## .... ............ .................. .......... ............
## See problems(...) for more details.

SOLUTION: Manually assign column types

01_load - Challenges and Solutions 3 (DELETE SLIDE)

CHALLENGE: NA strings (“NA”, “N/A”, “Unknown”, " "…)

SOLUTION:

Methods - Challenges and solutions - 02_clean

Patients data set:

  • Unwanted dirty/uniformative columns → select(-c(CAGE_YR, CAGE_MO, RPT_DATE,SYMPTOM_TEXT,LAB_DATA,OFC_VISIT, ER_VISIT, X_STAY, V_FUNDBY, BIRTH_DEFECT,SPLTTYPE, RECVDATE, RECOVD, L_THREAT))

  • NAs that should be interpreted as “no” → replace_na()

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    • Unwanted dirty/uniformative columns → select(-c(CAGE_YR, CAGE_MO, RPT_DATE … ))
    • NAs that should be interpreted as “no” → replace_na(ALLERGIES = “N”)
    • Row duplications → distinct()
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    Vaccines dataset:

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Methods - Challenges and solutions - 02_clean

Vaccine data set:

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  • Contains non-COVID19 vaccines → filter(VAX_TYPE == “COVID19”)
  • Contains vaccines of unknown manufacturer → filter(VAX_MANU != “UNKNOWN MANUFACTURER”)
  • Row duplications → distinct()
  • Duplicated IDs → add_count(VAERS_ID) %>% filter(n == 1) %>% select(-n)
  • Inconsistent naming of vaccines → rename()
  • Redundant and dirty columns → select(-c(VAX_NAME, VAX_LOT))

Symptoms dataset:

  • SYMPTOMVERSION1-5 columns are unneccessary → select(-c())
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Methods: Data augmentation

Challenges and solutions

Patients data set:

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02_clean - Challenges and Solutions 1 (DELETE SLIDE)

I am aware of how horrible this table is :/

CHALLENGE SOLUTION
Unwanted columns select(-c())
NAs that should be interpreted as “no” replace_na()
Row duplications distinct()
Individuals who got more than one vaccine type (generates noise) add_count(VAERS_ID) %>% filter(n==1) %>% select(-n)

Project methods - Challenges and solutions - 03_augment

Patients data set:

  • Columns containing long string descriptions → Make tidy categorical variables
    • ALLERGIES → HAS_ALLERGIES (Y/N)
    • CUR_ILL → HAS_ILLNESS (Y/N)
    • CUR_ILL → HAS_COVID (Y/N)
    • HISTORY → HAD_COVID (Y/N)
    • PRIOR_VAX → PRIOR_ADVERSE (Y/N)
    • OTHER_MEDS → >>>>>>> 2a99c43368ec3918981982f08c32e311f203710a
      • Columns containing long string descriptions → Make tidy categorical (Y/N) variables
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      ## # A tibble: 3 x 3
      ##   VAERS_ID OTHER_MEDS                     TAKES_ANTIINFLAMATORY
      ##   <chr>    <chr>                          <chr>                
      ## 1 0916983  <NA>                           N                    
      ## 2 0916988  Ibuprofen  PM the night before Y                    
      ## 3 0916996  Clobetasol, Benadryl           N
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Project methods - Challenges and solutions - 03_augment

Vaccine data set:

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  • Dirty, redundant and uninformative columns → select(-c(ALLERGIES, OTHER_MEDS … ))

Symptoms data set:

  • Too many symptoms and dirty → extract top 20 occurring symptoms and turn them into tidy categorical (TRUE/FALSE) columns
  • Calculate total number of symptoms per patient → mutate() to add column (N_SYMPTOMS)
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Methods: Data augmentation

Merging datasets

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Project methods - Challenges and solutions - 03_augment

Merged data sets:

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  • For visualizing, we need the wide format → inner_join(by = VAERS_ID)
  • For modelling, symptoms must be in long-format → pivot_longer() to create:
    • SYMPTOM column: top 20 symptom names
    • SYMPTOM_VALUE column: TRUE/FALSE
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Methods: Analysis

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03_augment - Challenges and Solutions 1 (DELETE SLIDE)

CHALLENGE: Some columns contain long string descriptions that need to be turned into something tidy

SOLUTION: Make categorical variable

03_augment - Challenges and Solutions 1 (DELETE SLIDE)

Example: ALLERGIES column:

Make categorical variable that states if patient has allergies or not:

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Exploratory data analysis

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  • Visualizations with ggplot()
  • Reduction of dimensionality (Principal Component Analysis) with prcomp()
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## # A tibble: 5 x 3
##   VAERS_ID ALLERGIES                                               HAS_ALLERGIES
##   <chr>    <chr>                                                   <chr>        
## 1 0916603  Diclofenac, novacaine, lidocaine, pickles, tomatoes, m… Y            
## 2 0916604  <NA>                                                    N            
## 3 0916660  Penicillin                                              Y            
## 4 0916685  none that I am aware of                                 N            
## 5 0917437  No known allergies                                      N

03_augment - Challenges and Solutions 1 (DELETE SLIDE)

Another example: OTHER_MEDS column

Detect individuals that have taken anti-inflammatory or steroid drugs before vaccine (not recommended):

Clean, categorial TAKES_ANTIINFLAMMATORY and TAKES_STEROID columns:

## # A tibble: 4 x 4
##   VAERS_ID OTHER_MEDS                           TAKES_ANTIINFLAM… TAKES_STEROIDS
##   <chr>    <chr>                                <chr>             <chr>         
## 1 0918421  1 aspirin a day 81 mg, levothyroxin… Y                 N             
## 2 0921732  Ibuprofen - PRN  States she does no… Y                 N             
## 3 0932980  Hydrocortisone 25mg daily.  Fludroc… N                 Y             
## 4 0934539  Singulair, Oxybutynin, Fosamax, Pre… N                 Y

03_augment - Challenges and Solutions 2 (DELETE SLIDE)

CHALLENGE: Symptoms are recorded in a way that makes later analysis difficult

## # A tibble: 5 x 6
##   VAERS_ID SYMPTOM1           SYMPTOM2        SYMPTOM3 SYMPTOM4         SYMPTOM5
##   <chr>    <chr>              <chr>           <chr>    <chr>            <chr>   
## 1 0916618  Injection site pa… Pain            <NA>     <NA>             <NA>    
## 2 0916619  Injection site pa… Menorrhagia     <NA>     <NA>             <NA>    
## 3 0916620  Arthralgia         Chills          Headache Mobility decrea… Myalgia 
## 4 0916620  Nausea             Pain in extrem… Pyrexia  <NA>             <NA>    
## 5 0916621  Chills             Fatigue         Headache Myalgia          <NA>
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Modelling and statistics

  • Logistic regression models with glm()
  • Proportions tests with chisq.test()

04_analysis_visualizations

04_analysis_visualizations - Age, sex and vaccine manufacturer distribution

04_analysis_visualizations - Age distribution

04_analysis_visualizations - Age manufacturer distribution

04_analysis_visualizations - Sex and vaccine manufacturer distribution

Sex distribution
SEX n
F 24070
M 8514
NA 828
Vaccine manufacturer distribution
VAX_MANU n
JANSSEN 1106
MODERNA 16253
PFIZER-BIONTECH 16053

04_analysis_visualizations - Days until onset of symptoms vs. Age Group

Hypothesis: two peaks corresponding to the innate and acquired immune response

04_analysis_visualizations - Age/sex vs. number of symptoms

04_analysis_visualizations - Vaccine manufacturer vs. number of symptoms

04_analysis_visualizations - Age vs. types of symptoms

04_analysis_visualizations - Sex vs. types of symptoms

04_analysis_visualizations - Vaccine manufacturer vs. types of symptoms

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04_analysis_regressions

04_analysis_modeling

Logistic regression: death ~ patient profile

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04_analysis_regressions

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04_analysis_visualizations - vaccine manufacturer vs. death

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04_analysis_regressions

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04_analysis_modeling

Logistic regression: death ~ patient profile

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## # A tibble: 7 x 6
##   term           estimate std.error statistic  p.value odds_ratio
##   <chr>             <dbl>     <dbl>     <dbl>    <dbl>      <dbl>
## 1 (Intercept)    -9.34      0.161    -58.0    0         0.0000876
## 2 SEXM            0.924     0.0573    16.1    2.18e-58  2.52     
## 3 AGE_YRS         0.0915    0.00207   44.2    0         1.10     
## 4 HAS_ALLERGIESY -0.100     0.0608    -1.65   9.82e- 2  0.904    
## 5 HAS_ILLNESSY    1.10      0.0664    16.6    6.60e-62  3.01     
## 6 HAS_COVIDY     -0.117     0.148     -0.791  4.29e- 1  0.890    
## 7 HAD_COVIDY      0.00915   0.193      0.0474 9.62e- 1  1.01

04_analysis_modeling

Logistic regression: death ~ patient profile

04_analysis_modeling

Logistic regression: death ~ symptoms

## # A tibble: 20 x 6
##   term          estimate std.error statistic  p.value odds_ratio
##   <chr>            <dbl>     <dbl>     <dbl>    <dbl>      <dbl>
## 1 (Intercept)     -2.01     0.0287    -70.1  0             0.134
## 2 HEADACHETRUE    -1.67     0.156     -10.7  7.92e-27      0.188
## 3 PYREXIATRUE     -0.429    0.112      -3.82 1.34e- 4      0.651
## 4 CHILLSTRUE      -1.21     0.171      -7.11 1.17e-12      0.298
## 5 FATIGUETRUE     -0.367    0.115      -3.19 1.41e- 3      0.693
## 6 PAINTRUE        -0.913    0.153      -5.98 2.17e- 9      0.401
## 7 NAUSEATRUE      -0.621    0.139      -4.46 8.17e- 6      0.538
## 8 DIZZINESSTRUE   -2.17     0.193     -11.2  2.87e-29      0.114
## # … with 12 more rows

04_analysis_modeling

Logistic regression: death ~ symptoms

04_analysis_modeling

Many logistic regressions: each symptom ~ takes anti-inflamatory

## # A tibble: 20 x 9
##   SYMPTOM  estimate std.error statistic p.value conf.low conf.high odds_ratio
##   <chr>       <dbl>     <dbl>     <dbl>   <dbl>    <dbl>     <dbl>      <dbl>
## 1 HEADACHE  -0.170     0.0954    -1.79   0.0742   -0.361    0.0133      0.843
## 2 PYREXIA    0.0734    0.0967     0.760  0.448    -0.120    0.259       1.08 
## 3 CHILLS    -0.0727    0.103     -0.703  0.482    -0.280    0.126       0.930
## 4 FATIGUE    0.0226    0.102      0.221  0.825    -0.183    0.219       1.02 
## 5 PAIN       0.0190    0.106      0.179  0.858    -0.194    0.222       1.02 
## # … with 15 more rows, and 1 more variable: identified_as <chr>

04_analysis_modeling

Many logistic regressions: each symptom ~ takes anti-inflamatory

04_analysis_tests

04_analysis_tests

Chi-squared contingency table tests

04_analysis_clustering

04_analysis_clustering - Important tools used

Important verbs and tools used:

  • prcomp()
  • kmeans()
  • tidymodels: (used for what?)

04_analysis_clustering - PCA biplot

04_analysis_clustering - Rotation matrix

04_analysis_clustering - Scree plot

Conclusion and discussion